Ramona O. Hopkins

Severe anoxia with and without concomitant brain atrophy and neuropsychological impairments.

Significant anoxia may cause a variety of neuropathologic changes as well as cognitive deficits. We have recently seen 3 patients who have suffered severe anoxic episodes all with initial Glasgow Coma Scores (GCS) of 3 with sustained coma for 10-14 d. All 3 patients had extended hospitalizations and rehabilitation therapy. A neuropsychological test battery was administered and volumetric analyses of MRI scans were carried out in each case at least 6 mo postinjury. Two of the patients display distinct residual cognitive and neuropathologic changes while 1 patient made a remarkable recovery without evidence of significant morphological abnormality. These three cases demonstrate, that even with similar admission GCS, the outcome is variable and the degree of neuropsychological impairment appears to match the degree of morphologic abnormalities demonstrated by quantitative MR image analysis. An important finding of this study is that even though subjects with an anoxic insult exhibit severe cognitive and memory impairments along with concomitant morphologic changes, their attention/concentration abilities appear to be preserved. MR morphometry provides an excellent means by which neural structural changes can be quantified and compared to neuropsychological and behavioral outcomes.

Memory for novel and familiar spatial and linguistic temporal distance information in hypoxic subjects.

Hypoxia is known to cause damage to the hippocampus as well as memory impairments in humans. Subjects who have experienced a hypoxic episode and age-, gender-, and education-matched control subjects were tested for memory for spatial and linguistic temporal distance information using sentences and spatial locations. Each test contained a familiar component based on information that is meaningful and is thought to be stored as part of the knowledge system (prior knowledge) as well as a novel component based on new information. Subjects were presented a list of eight-word sentences or eight spatial locations (Xs) on a grid on a Macintosh computer and tested for memory for temporal distances. Temporal distance is defined as the number of items that occur between the two test items, in the study phase. Compared to control subjects, hypoxic subjects were impaired across all temporal distances on the novel spatial and linguistic tasks. As the temporal distance increased, hypoxic subjects showed some improvement in memory performance. In addition, memory of familiar temporal distance information was also assessed. Hypoxic subjects were impaired, compared to control subjects, for familiar temporal distance information. For hypoxic subjects there was a proportionally greater impairment for novel compared to familiar spatial and linguistic temporal distance information. There was a significant difference in their performance on the familiar temporal distance tasks compared to their performance on the novel tasks. Prior knowledge appears to attenuate the deficits seen in the familiar temporal distance tasks. It appears that hypoxia may cause more selective damage to the hippocampus and this damage is sufficient to produce profound memory impairments for primarily novel and less severe memory impairments for familiar spatial and linguistic temporal distance information.

Assessing neurocognitive outcomes after critical illness: are delirium and long-term cognitive impairments related?

Purpose of reviewCritically ill patients have a high risk of developing neurologic dysfunction including delirium and long-term cognitive impairment. In this paper we examine possible relationships between delirium and long-term cognitive impairments and explore this in the context of critical illness. Recent findingsCritical illness and its treatment can lead to neurologic morbidity including neuropathological abnormalities, delirium, and cognitive impairments. The association between delirium and long-term cognitive impairments has been shown in a number of populations. Among intensive care unit cohorts, delirium appears to be one of many possible causes of cognitive impairments and may be a leading modifiable cause. The mechanisms of both delirium and intensive care unit related cognitive impairment remain unclear, although a variety of common mechanisms have been proposed. SummaryPotential neurologic consequences of critical illness include delirium and long-term cognitive impairments. Defining the extent of their association in intensive care unit cohorts is an important research priority due to the high prevalence of delirium and persistent cognitive impairments in critically ill patients. Future research should focus on strategies for the early identification of delirium and cognitive impairments, elucidating mechanisms of brain injury, and the development and implementation of therapeutic modalities designed to prevent or decrease delirium and cognitive morbidity.

The role of future longitudinal studies in ICU survivors: understanding determinants and pathophysiology of brain dysfunction.

Purpose of reviewRecent investigations demonstrate that most critical care survivors face significant brain-related morbidity including neurocognitive deficits. While current data on neurocognitive outcomes after critical illness are intriguing, gaps in the literature far exceed what we have learned to date. In this paper, we examine important areas of investigation heretofore unaddressed and propose directions for clinically oriented outcomes research. Recent findingsNeurocognitive impairments after critical illness, which affect multiple cognitive domains, may improve during the first 12 months after ICU discharge but may persist in many patients for years. These impairments appear to be independent of traditional measures of severity of critical illness or age, and risk factors for and mechanisms of injury are currently being defined. SummaryOver the last decade, ICU-related cognitive impairment has been identified as a significant public health problem and has become the focus of intense investigation by researchers around the world. While substantial work has been done to date, vitally important questions remain. Future research should evaluate the mechanisms of and risk factors for brain injury, the natural history of neurocognitive dysfunction, structural and functional brain-imaging studies, and therapeutic modalities designed to prevent or decrease neuropsychological disability.

Neuropsychological impairments following hantavirus pulmonary syndrome

Recently an outbreak of acute respiratory infection associated with the hantavirus occurred in the southwestern United States. Hantavirus pulmonary syndrome (HPS) is a life threatening illness that carries with it a high mortality rate. Patients with HPS experience prolonged periods of hypoxemia requiring mechanical ventilation and treatment in intensive care units. We have recently seen 2 survivors of HPS. A neuropsychological test battery was administered immediately following their acute hospitalization and at 1 year postrecovery from HPS. Both patients exhibited cognitive impairments immediately following HPS as well as persistent cognitive impairments at 1 year. The cognitive impairments seen in these two HPS survivors are similar to those seen in other patients who have experienced brain anoxia, including memory impairments. It is also possible that hantavirus may directly cause brain injury with concomitant cognitive impairments. Additional research needs to be carried out in order to determine the extent and severity of the cognitive impairments in survivors of HPS.

Three Dimensional Image Reconstruction of Neuroanatomical Structures: Methods for Isolation of the Cortex, Ventricular System, Hippocampus, and Fornix

Magnetic Resonance (MR) imaging allows volumetric quantification of a variety of neuroanatomical structures using two dimensional (2D) images as well as three-dimensional (3D) reconstruction of the brain and any of its constituent parts. Three-dimensional analysis permits integration of the neuroanatomical changes which occur in pathologic states, with the cognitive and behavioral changes elucidated through neuropsychological assessment. This paper describes uniform methods for 3D neuroanatomical isolation of the neocortex, ventricular system, and hippocampus in both normal and pathologic states. The 3D methods are described in detail using two different software programs, ANALYZE and IMAGE. Three-dimensional neuroanatomical reconstructions were carried out on a patient who sustained a very severe traumatic brain injury. The 3D image analysis in the patient with traumatic brain injury, revealed structural changes in frontal and temporal cortex, ventricular dilation, and hippocampal atropy. The neuropsychological impairments in this patient, were consistent with the observed neuroanatomical changes revealed on 3D image reconstruction. This technology permits precise determinations of the extent and severity of the neuroanatomical changes which follow neurological injury disease.

Critical illness brain syndrome (CIBS)

To the Editor: Recent studies in Critical Care Medicine remind us that patients’ quality of life is reduced following critical illness (1–4). Most authors focus on long-term physical, neurocognitive, psychiatric, and psychological outcomes, and this is important because these factors contribute to the patient’s quality of life after the illness. What is less clear is to what degree these factors are a consequence of secondary brain injury acquired during the period of critical illness. For the peripheral nervous system, it has been demonstrated that critical illness polyneuropathy (CIP) is an example of multifactorial etiology causing a recognizable syndrome characterized by electrophysiological and pathologic evidence for loss of axons (5). As with CIP, it seems likely that for the central nervous system, independent of any primary injury, diffuse secondary brain injury contributes substantially to the outcome. General intensive care unit patients with no initial brain pathology at all frequently display cognitive deficits after discharge (4). Patients with traumatic brain injury often have cognitive problems that far outweigh those that would be predicted by their initial clinical status and neuroimaging. Analogous to CIP, it is often uncertain whether neurologic deficits are the result of hypoxic brain damage or because of metabolic, infectious, toxic, or nutritional complications. These multiple pathologic processes probably induce loss of axons, neurons, and ramification of the dendritic tree, which constitutes the functional circuits of the human brain. In contrast to CIP, there is no easy way to quantify neuroaxonal loss in the central nervous system. Conventional brain imaging does not readily allow for the detection of diffuse axonal loss, and an electroencephalogram is most likely to reveal unspecific slowing of cerebral activity. We believe that there is a need to define a syndrome that has such a major impact on a patient’s function, independence, and social life. Therefore, we would like to suggest the adoption of a holistic approach by summarizing all these factors under a single umbrella: critical illness brain syndrome (CIBS). This will, we believe, aid the intensive care community to focus on the multiple neurologic, cognitive, psychological, and psychiatric sequelae of the management of a critically ill patient (1–4). Crucially, we are seeing great advances in multiple modal neuromonitoring facilities, particularly in the development of novel biomarkers of brain injury that might be able to detect and quantify neuroaxonal degeneration. Additionally, advanced imaging techniques may increase the sensitivity for detecting diffuse axonal loss and allow quantifying brain atrophy in these patients. These developments may enable us to test hypotheses on a causative relationship between physiologic derangements, drug toxicity, and current management strategies to the development of a CIBS. In the future, it may be possible to guide management by evidence-based strategies to minimize the risk of the development of a CIBS, rather than adopting a “wait and see” strategy in the sedated and ventilated patient. We would like to propose the term critical illness brain syndrome (CIBS) to describe those patients who develop disability-related secondary brain damage occurring during periods of critical illness.